Osteoporosis is recognized as a major public health problem in Western countries, especially among elderly white women. See Cummings, S. R. et al, Epidemiol. Rev., 7:178 to 208 (1985). Postmenopausal osteoporotic fractures affect 1.5 million people each year. About 300,000 new cases of osteoporotic hip, 650,000 of vertebrae, and 200,000 of distal forearm fractures are reported annually in the USA. Mortality in the first year after hip fractures reaches 20%. See Cooper, C. et al, Amer. J. Epidem., 1001 to 1005 (1993) and Riggs, B. L., West. J. Med., 154:63 to 67 (1991). The estimated direct cost for treatment of these patients in the USA exceeds $6 to $10 billion annually. See Holbrook, T. L. et al, Lancet, 2:1046 to 1049 (1988) and the Riggs, B. L. reference cited above. Half of the survivors are unable to walk unassisted and 25% are confined to long term care in a nursing home.
Epidemiological and clinical observations strongly indicate that osteoporosis and fractures are related to aging. See once again Cummings, S. R. et al, Epidemiol. Rev., 7:178 to 208 (1985) and also Cummings, S. R. et al, Arch. Intern. Med., 149:2445 to 2448 (1989) and Ross, P. D. et al, Am. J. Epidem., 133:801 to 809 (1991). Particularly rapid loss of bone mass is noted in the first decade after menopause, and implicates estrogen deficiency as an etiological factor.
One of the first observations by Albright more than 50 years ago noted that 40 out of 42 patients with osteoporotic fractures were postmenopausal women. See Albright, F. et al, J.Am.Med.Ass., 116:2465 to 2474 (1941). Indeed the incidence rate of hip fractures rises dramatically with age after 50, and increases about 3 times after 80; see once again Cummings, S. R. et al, Epidemiol. Rev., 7:178 to 208 (1985). It is estimated that adult white women who, on average, will live to age 80 have a 15% lifetime risk of suffering a hip fracture, but in contrast, a white man who has a 75-year life expectancy has only a 5% lifetime chance of a hip fracture. The incidence of limb fractures rises with age, from approximately 7.3 per thousand to about 40 per thousand at ages 45 and 85, respectively. See Henert, A. M. et al, Am. J. Epidem. 132:123 to 135 (1990).
Prevention is likely to remain the most effective method of dealing with osteoporosis. Estrogens can protect the patient against osteoporosis. Hormone replacement therapy starting shortly after menopause prevents rapid bone loss and leads to reduction in the fracture risk of up to 60%. Unfortunately there are side effects and other risk factors associated with using estrogens in hormone replacement to prevent postmenopausal osteoporosis.
Weak non-steroidal synthetic estrogens, tamoxifen, toremifene, etc., that are used for breast cancer therapy, have a beneficial effect on bone formation. None of these compounds, however, has proven to be satisfactory in treating osteoporosis.
Diet has also been considered in the control of osteoporosis. Most diet recommendations for the prevention or control of osteoporosis center on increasing the intake of calcium, magnesium, Vitamin D, fluorides, and restriction of the amount of salt, caffeine, alcohol, and consumed animal protein. It is known in the traditional Japanese diet that the average intake of soy products for women amounts to more than 55 g/day. Several studies have indicated that the incidence of hip fracture in Japan is considerably lower than in Western countries. In Hawaii, hip fracture rates among persons of Japanese ancestry were approximately half that of Caucasians.
It is well known that the diet in Japan includes intake of large amounts of soy products. According to The Lancet, Vol. 339, p. 1233 (16 May 1992), H. Adlercreutz et al, Dietary Phytoestrogens and the Menopause in Japan, the diet high in soy may be the reason why menopausal symptoms are much less frequent in Japan than in Western countries. The Lancet reported that the urine of several Japanese men, women, and children was analyzed and the urine was found to contain a high amount of phytoestrogens. There is no mention or suggestion in this reference, however, of specifically avoiding osteoporosis thanks to a high soy diet.
The phytoestrogens are diphenolic plant compounds that are somewhat related structurally to the mammalian sex hormone: 17-beta-estradiol. See Setchell, K. D. R., et al Am. J. Clin. Nutr., 40:569 to 578 (1984). Two chemical classes of phytoestrogens are abundant in soybeans, total soy products, and soy protein isolates. Those two classes are coumestrol and isoflavones. The latter class includes daidzein, genistein, glycitein, as well as their glycoside and acetylated forms. The level of phytoestrogens in total soybeans and their bioavailability are relatively high, and their metabolism is similar to that of endogenous sex hormones. A diet rich in soybeans may affect estrogen metabolism. See Adlercruetz, H. et al, J. Steroid. Biochem., 24: pp 289 to 296 (1986).
Phytoestrogens and their metabolites interact with specific cell receptors and compete with endogenous hormone molecules [see Folman, Y. et al, J. Endocr., 44:213 to 218 (1969)], but the biological estrogen-like effect of these compounds is relatively weak. See Kaziro, R. et al, J. Endocr., 103:395 to 399 (1984) and Tang, B. Y. et al, J. Endocr. 85:291 to 297 (1980).
Phytoestrogens can induce two different effects in an organism. When the level of endogenous sex hormones is relatively high, the antiestrogenic effect prevails. There are several mechanisms of antiestrogenic activity of phytoestrogens, including feedback inhibition at the hypothalamus and pituitary glands, and competition and blockade of cell receptors. It has been observed that a phytoestrogen- and lignan-rich diet is associated with the reduction of free plasma estradiol, and the risk of breast cancer. See Adlercreutz, H. et al, J. Steroid. Biochem., 27:1135 to 1144 (1987) and Mousavi, Y. et al, Steroids, 58:301 to 304 (1993). On the other hand in postmenopausal women, phytoestrogens can provoke an estrogenic response. See Adlercruetz, H. et al, Lancet, 339:1233 (1992). This dual effect of weak estrogens is perceptible, and well known "partial" antigens such as Tamoxifen have these properties.